Correction to: Fire spalling sensitivity of high-performance concrete in heated slabs under biaxial compressive loading

The article ''Fire spalling sensitivity of high-performance concrete in heated slabs under biaxial compressive loading'', written by "Francesco Lo Monte, Roberto Felicetti, Chiara Rossino", was originally published electronically on the publisher's Internet portal (currently SpringerLink) on 25 January 2019 without open access

Switching the three-component Biginelli-like reaction conditions for the regioselective synthesis of new 2-amino[1,2,4]triazolo[1,5-a]pyrimidines

: Among the eight different triazolopyrimidine isomers existing in nature, 1,2,4-triazolo[1,5-a]pyrimidine (TZP) is one of the most studied and used isomers in medicinal chemistry. For some years, our group has been involved in developing regioselective one-pot procedures for the synthesis of 2-amino-7-aryl-5-methyl- and 2-amino-5-aryl-7-methyl-TZPs of interest in the preparation of antiviral agents. In this work, taking advantage of a Biginelli-like multicomponent reaction (MCR), we report the identification of finely tunable conditions to regioselectively synthesize C-6 ester-substituted amino-TZP analogues, both in dihydro and oxidized forms. Indeed, the use of mild acidic conditions is strongly directed toward the regioselective synthesis of 5-aryl-7-methyl C-6-substituted TZP analogues, while the use of neutral ionic liquids shifted the regioselectivity towards 7-aryl-5-methyl derivatives. In addition, the novel synthesized scaffolds were functionalized at the C-2 position and evaluated for their antiviral activity against RNA viruses (influenza virus, flaviviruses, and SARS-CoV-2). Compounds 25 and 26 emerged as promising anti-flavivirus agents, showing activity in the low micromolar range

MiR126-targeted-nanoparticles combined with PI3K/AKT inhibitor as a new strategy to overcome melanoma resistance

Metastatic melanoma poses significant challenges as a highly lethal disease. Despite the success of molecular targeting using BRAFV600E inhibitors (BRAFis) and immunotherapy, the emergence of early recurrence remains an issue and there is the need for novel therapeutic approaches. This study aimed at creating a targeted delivery system for the oncosuppressor microRNA 126 (miR126) and testing its effectiveness in combination with a phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT) inhibitor for treating metastatic melanoma resistant to BRAFis. To achieve this, we synthesized chitosan nanoparticles containing a chemically modified miR126 sequence. These nanoparticles were further functionalized with an antibody specific to the chondroitin sulfate proteoglycan 4 (CSPG4) melanoma marker. After evaluation in vitro, the efficacy of this treatment was evaluated through an in vivo experiment using mice bearing resistant human melanoma. The co-administration of miR126 and the PI3K/AKT inhibitor in these experiments significantly reduced tumor growth and inhibited the formation of liver and lung metastases. These results provide evidence for a strategy to target an oncosuppressive nucleic acid sequence to tumor cells while simultaneously protecting it from plasma degradation. The system described in this study exhibits encouraging potential for the effective treatment of therapy-resistant metastatic melanoma while also presenting a prospective approach for other forms of cancer

Fire spalling sensitivity of high-performance concrete in heated slabs under biaxial compressive loading

Explosive spalling of concrete exposed to fire consists in the violent expulsion of shards from the hot surface due to the interaction between cracking and pore pressure build-up. Fire spalling relevantly increases the overall thermal damage of a structure exposed to fire, thus leading to much higher costs in the repair intervention, and in some cases it can even jeopardize the structural stability due to loss of reinforcement protection and reduction of the bearing cross-sections. High-performance concrete is particularly sensitive to spalling phenomenon due to inherent material features, such as the unstable fracture behaviour and the low permeability (favouring high values of pore pressure). In this context, an experimental campaign has been carried out on high-performance concrete (fc ≈ 60 MPa with silico-calcareous aggregate), without or with one of three different fibre types (steel fibre, monofilament or fibrillated polypropylene fibres). Tests were performed by means of a special test setup developed at Politecnico di Milano, based on slabs (800 × 800 × 100 mm) subjected to Standard Fire at the bottom and to biaxial compressive loading in the mid-plane, while monitoring pore pressure, temperature and deflection. Explosive spalling was observed in both plain concrete slabs and in one of the two slabs with steel fibre, this casting some doubts on the use of steel fibre alone against spalling. No detachment was observed when polypropylene fibre was added to the mix

Leukocytoclastic vasculitis associated with multifocal sensory neuropathy responsive to intravenous immunoglobulins: a case report

Leukocytoclastic vasculitis (LCV) is a common form of small-vessel vasculitis, which commonly presents as palpable purpura or petechiae, caused by deposition of circulating immune complexes on vessels walls that attracts granulocytes which damage the vascular endothelium and leading to erythrocytes extravasation. The skin is the most commonly involved organ, but also renal, gastrointestinal, pulmonary, cardiovascular and neurological systems may be affected. Skin lesions may be the initial signs of systemic vasculitis. Systemic symptoms may be present, such us fever, myalgia, abdominal pain and arthralgia. The presence of neuropathy/mononeuritis multiplex is expression of severe vasculitic involvement. Herein, we describe the case of a patient with leucocytoclastic vasculitis associated to sensitive neuropathy, responsive to intravenous immunoglobulins (IVIg) therapy, after the failure of classic systemic treatments

HPC Subjected to High Temperature: A Study on Intrinsic and Mechanical Damage

Heat-exposed High-Performance Concrete (HPC) has been the subject of relatively few studies focused on the relationship between the chemo-physical processes occurring in concrete constituents (microscopic level) and concrete mechanical properties (macroscopic level). In order to investigate the correlation between the intrinsic damage and the mechanical damage induced by heat exposure, eleven concrete mixes have been investigated, differing for: compressive strength (fcm,cube ≥ 45, 70, 95 MPa), aggregate type, fiber type (polymeric and metallic) and fiber content. The microstructural and mechanical characterization was carried out on concrete specimens before and after being exposed to 105, 250, 500 and 750°C. The results show that using different experimental techniques at the microstructural level allows to monitor the development of microcracks, whose size is similar to that of macropores. This behavior at the nano-, micro-level is reflected by the post-peak branch of the stress-strain curve at the macro-level. This extensive investigation allows to understand concrete mechanical decay due to heating on the basis of microstructural observations, paving the way to mix optimization for high temperature and fire

One year in review 2019: vasculitis

Systemic vasculitis are disabling complex disorders potentially involving any organ and system. Tremendous efforts have been made recently in this field with novel insights into pathogenesis and new therapy in the pipeline. Following the previous annual reviews of this one year in review series, in this paper we provide a critical digest of the most recent literature regarding pathogenesis, clinical manifestations and therapy, with the ultimate aim of addressing whether the existing data may open new avenues for precision medicine in these disorders